Background: A previous single-arm Phase 2 study (

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), evaluated the ability of tumor-specific idiotype (ID) conjugated to keyhole limpet hemocyanin (KLH) administered with granulocyte-monocyte colony-stimulating factor - GM-CSF (BiovaxID vaccine) to induce complete remission (CR) and molecular remission (MR) in follicular NHL patients in first CR after chemotherapy. We reported (ASH 2005, Abstr 2441) that at 9.2 years follow-up, disease free survival (DFS) and overall survival (OS) were 45% and 95%, respectively; median DFS was 8.0 years. To date, there have been no additional reported mortalities in this cohort. Although these data are promising, improvements in the treatments and increasing survival for patients with follicular lymphoma have necessitated additional rigor in the evaluation of overall safety and overall risk-benefit. The ongoing Phase 3 study that opened in 2000 by the NCI is designed to evaluate the impact of this vaccine on DFS in previously untreated subjects who have attained CR/Cru. As of August 2007, 231 subjects have been enrolled to receive chemotherapy and 176 have been randomized to receive vaccine (ID-KLH or KLH-KLH).

Methods: Since Phase 3 trial inception in 2000, SAEs have been reported through a pharmacoviligance group and identified according to time period on the study (i.e. during chemotherapy, during vaccine, after vaccine, or unknown), causality, and relatedness to study agent.

Results: As of August 2007, 32 SAEs have been reported in the BV301 trial, 7 of which occurred during the vaccination segment of the study. At a blinded interim analysis of the Phase 3 safety data, of the 7 SAEs reported during the vaccine segment of the study, 3 are considered unlikely to be related to the study agent (chest pain, compression fracture, herpes zoster), 2 possibly related (arrhythmia supraventricular, chest pain), 1 unrelated (vomiting), and 1 unknown (febrile neutropenia). The 1 SAE, cerebral ischaemia, that occurred post vaccine is considered unrelated to the study agent.

Conclusions: Additional follow-up on the Phase 2 patients is needed, as well as similar analyses in other cohorts. Blinded Phase 3 safety data shows a positive safety profile for BiovaxID. Unblinded safety data will be needed to determine the final efficacy and safety profile.

Author notes

Disclosure: Employment: Stergiou, A.M., Casicano R. & Jaffee, M.A. are employed by Biovest International. Neelapu, S.S. & Kwak, L.W. are employed by University of Texas MD Anderson Cancer Center. Consultancy: Neelapu, S.S. & Kwak, L.W. are consultants for Biovest International.

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